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Improved in vitro dissolution parameters and in vivo hypolipidemic efficiency of atorvastatin calcium through the formation of hydrophilic inclusion complex with cyclodextrins
Author(s) -
Hussein Amal K.,
Ibrahim Mohamed A.,
Amin Mohamed A.,
Ahmed Osama A.A.,
Afouna Mohsen I.
Publication year - 2011
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20439
Subject(s) - dissolution , chemistry , solubility , in vivo , cyclodextrin , aqueous solution , dissolution testing , molar ratio , inclusion (mineral) , nuclear chemistry , chromatography , calcium , in vitro , organic chemistry , biochemistry , mineralogy , catalysis , biopharmaceutics classification system , microbiology and biotechnology , biology
An aim of the present study was to improve the dissolution of the inherently low water solubility hypolipidemic agent, Atorvastatin calcium (ATC), through the preparation and characterization of ATC with cyclodextrins (CDs) inclusion complexes employing different techniques. A second goal was to study the in vivo hypolipidemic efficacy of ATC‐complexes with enhanced dissolution characteristics. Inclusion complexation of ATC with β‐cyclodextrin (β‐CD) and hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) was evaluated in aqueous and solid states. ATC formed inclusion complexes with β‐CD and HP‐β‐CD depending to a great extent upon ATC ionization state. Evaporation and freeze‐drying were the most efficient techniques to achieve complexation. In contrast, kneading was an inefficient tool to create true inclusion complexes, which could reflect the hindrance of drug–CDs interactions in the semisolid medium. The ATC:CD ratio of 1:2 showed better dissolution characteristics compared to a 1:1 ratio. Moreover, the in vivo hypolipidemic activities of ATC‐CDs (β‐CD and HP‐β‐CD) complexes were greater ( P <0.05) than the other investigated formulations. Thus the nature of the carrier did not play a critical role in the dissolution characteristics of the inclusion system. In contrast, the carrier molar ratio, and the employed complexation technique were found to be key factors in enhancing the ATC dissolution rate, yielding performances as well as the in vivo hypolipidemic efficacies. Drug Dev Res 72: 379–390, 2011. © 2011 Wiley‐Liss, Inc.